High Salt Cross-Protects Escherichia coli from Antibiotic Treatment through Increasing Efflux Pump Expression

Environmental stresses often co-occur when bacteria encounter antibiotic treatment inside the human body. The cellular response to environmental stressors can alter the global gene expression pattern of bacteria. However, the relationship between the cellular stress response and antibiotic susceptibility remains poorly understood. Here we studied the effect of high salt, an important environmental stress condition inside the human body, on bacterial susceptibility to antibiotics. We found that high salt reduces the susceptibility of Escherichia coli to tetracycline and chloramphenicol, leading to a cross-protection effect. The cross-protection effect originates from the increased AcrAB-TolC efflux pump expression level under high-salt conditions. Our study demonstrates that stress-induced gene expression alterations can cross-protect bacteria from antibiotic treatment and should thus be considered when investigating antibiotic susceptibility and applying antimicrobial treatment. IMPORTANCE Environmental stresses often co-occur when bacteria confront antibiotic treatment. We provide a clear example that a natural stress condition (high salt) can cross-protect bacteria from antibiotic treatment by triggering the bacterial stress response program (elevated AcrAB-TolC efflux pump expression). Our study highlights the importance of taking the co-occurrence of bacterial environmental stresses into consideration when investigating antibiotic susceptibility and applying antimicrobial treatment.